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The Journal of Neuroscience, October 15, 2001, 21(20):7881-7888

Therapeutic Efficacy in Experimental Polyarthritis of Viral-Driven Enkephalin Overproduction in Sensory Neurons

Joao Braz¹, Caroline Beaufour¹, Anne Coutaux², Alberto L. Epstein³, François Cesselin¹, Michel Hamon¹, and Michel Pohl¹

¹ Institut National de la Santé et de la Recherche Médicale U288, NeuroPsychoPharmacologie Moléculaire, Cellulaire, et Fonctionnelle and ² Service de Rhumatologie, Hôpital Pitié-Salpêtrière, 75013 Paris, France, and ³ Centre de Génétique Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 106, Université Claude Bernard Lyon 1, 69622 Villeurbanne, France

Rheumatoid arthritis is characterized by erosive inflammation of the joints, new bone proliferation, and ankylosis, leading to severely reduced locomotion and intense chronic pain. In a model of this disease, adjuvant-induced polyarthritis in the rat, neurons involved in pain transmission and control undergo plastic changes, especially at the spinal level. These changes affect notably neurons that contain opioids, such as enkephalins deriving from preproenkephalin A (PA) precursor protein. Using recombinant herpes simplex virus containing rat PA cDNA, we enhanced enkephalin synthesis in sensory neurons of polyarthritic rats. This treatment markedly improved locomotion and reduced hyperalgesia. Furthermore, the progression of bone destruction slowed down, which is the most difficult target to reach in the treatment of patients suffering from arthritis. These data demonstrate the therapeutic efficacy of enkephalin overproduction in a model of systemic inflammatory and painful chronic disorder.

Key words: proenkephalin A overproduction; dorsal root sensory ganglia neurons; polyarthritic rats; reduced hyperalgesia; improved polyarthritis-related disability; limited joint destruction

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21207881-08$05.00/0

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